 Keratins are a diverse group of structural proteins
that form the intermediate filament network
responsible for maintaining the structural integrity
 There are around 30 families of keratin proteins
divided into two groups namely acidic and basic
which are arranged in pairs.
 A total of 54 functional genes exist which codes
for these keratin families.
3.  The expression of specific keratin genes is
regulated by the differentiation of epithelial cells
within the stratifying squamous epithelium.
 Keratins and certain keratin associated proteins are
useful as markers of differentiation because their
expression is both region and differentiation
4.  Most of the eukaryotic cells are composed of
cytoskeleton which is made of three components
microfilaments, intermediate filaments, and
 Among the various families and sub-families of
intermediate filament proteins, keratin is an
important type due to its high molecular diversity.
 Each keratin is characterized by a chain of amino
acids as the primary structure, which varies in the
number and sequence of amino acid as well as in
polarity, charge and size.
 The amino acid sequence of a keratin influences
the properties and function of the keratin
6.  Post translational modifications such as the
formation of disulphide bonds, phosphorylation
and glycosylation can influence the conformation
of the molecule and formation of keratin
 Keratin filaments have a tripartite secondary
structure consisting of an N-terminal head
domain, a central α-helical rod domain and C-
terminal tail domain.
7. The keratins are broadly divided into:
 Primary keratins are those keratins which are
always synthesized by the epithelial cells on a
regular basis, e.g., K8/18 in simple epithelia, K5/14
in stratified epithelia.
 Secondary keratins are those types of keratins
which are produced by the epithelial cells in
addition to or instead of primary keratins, e.g.,
K7/19 in simple epithelia, K15, and K6/16 in
8. Based on distribution:
 Soft keratin: Found in the epidermis of skin in
the form of flattened non-nucleated scales that
slough continually. The disulfide links are fewer in
number which allows some stretching but returns
to normal upon relaxation of tension.
 Hard keratin: These are mainly found in nail, hair
cortex, hair cuticle; the keratin type seen at these
sites have very little flexibility owing to the
presence of many cysteine disulfide crosslinks.
9. Based on X-ray diffraction pattern:
 Alpha : The X-ray diffraction pattern of this type
resembles that of α-helix . The α-helix is right
handed and has 3.6 residues per turn. The
hydrogen bonding occurs within one polypeptide
 Beta : The helix is right-handed with an average
of 6 residues. The hydrogen bonding occurs
between neighbouring polypeptide chains.
10. Based on amino acid sequence
 Type I family includes keratins numbered 9-20
which are composed of acidic proteins.
 Type II family includes keratins numbered 1-8
which are composed of basic proteins.
11. Based on molecular weight:
 Low molecular weight keratins: Include keratins
with a molecular weight of 40kDa. These keratins
are mainly distributed in glandular and simple
 Intermediate molecular weight keratins: Include
keratins with a molecular weight intermediate
between 40kDa and 57kDa and are found in
 High molecular weight keratins: Include keratins
with a molecular weight of 57kDa and are seen in
keratinized stratified epithelia.
 Keratins fundamentally influence the architecture
and mitotic activity of the epithelial cells.
 Keratins and associated filaments provide a
scaffold for epithelial cells and tissues to sustain
mechanical stress, maintain their structural
integrity, ensure mechanical resilience, to protect
against variations in hydrostatic pressure and
establish cell polarity.
13.  Keratins and its filaments are involved in cell
signalling, cell transport, cell compartmentalization
and cell differentiation.
 Keratin filaments also influence cell metabolic
processes by regulating protein synthesis and cell
 Keratins may also be involved in the transport of
membrane bound vesicles in the cytoplasm of the
14. Factors regulating Differentiaition
 Growth factors like epidermal growth factor,
transforming growth factor alpha and beta
 Role of adjacent mesenchymal tissue
 Components of extracellular matrix
15. Effect of Retinoids on various keratins
K1/10 Reduced expression
K13/19 Increased expression
K5, K16, K17 Slightly downregulated
K4,K5, K14 Not affected
Filaggrin Reduced expression
Cornified cell envelope Suppressed
Desmosomes Reduced in number
16. Keratin distribution in epithelia
K5 / K14 Basal layer – keratinizined & non-
keratinized stratified epithelium
K1 / K10 Keratinized epidermis
K6 / K16 Spinous layer - keratinized mucosa
K4 / K13 Intermediate layer – non keratinized
K19 Basal layer – non keratinized epithelium
K9 Suprabasal layer – palmar & plantar
18. K8 & K18
 Keratins K8 & K18 are co-expressed and constitute
the primary keratin of simple epithelial cells.
 They are also the sole keratins of hepatocytes,
acinar cells of pancreas and proximal tubular cells
 They are the first keratins to appear in
19. K7 & K19
 They are the secondary or additional keratins of
simple epithelial cells.
 They are expressed notably in ductal epithelia of
small and large intestines, gastric foveolar
epithelium, mesothelium, urothelium, as well as
basal cells of non keratinizing stratified squamous
20.  They are frequently co-expressed.
 Type I keratin K19 is the smallest keratin.
 They are used as tumour markers.
 K20 is the simple epithelial keratin with most
restricted expression pattern.
 They are expressed in the gastric foveolar
epithelium, small and large intestinal epithelium,
urothelium and merkel cells.
 K20 positivity is predictive of a primary tumour in
the gastrointestinal or pancreatobiliary tract.
22. K5 & K14
 K5 & K14 form the primary keratin pair of
keratinocytes of stratified squamous epithelia,
including the epidermis and mucosal non
keratinizing stratified squamous epithelia.
 In the follicular outer root sheath they are
uniformly expressed throughout all layers.
23.  Ultrastructurally, K5/K14 keratin filaments are
bundled as tonofilaments and attached to
desmosomes and hemidesmosomes.
 Mutations of the K5 / K14 gene is responsible for
the blistering disease – Epidermolysis bullosa
 K15 keratin is a basal keratinocyte keratin and hair
follicle stem cell marker.
 In comparison to K5 and K14, K15 is completely
restricted to the basal cell layer of stratified
 It is also expressed in the basal keratinocytes of
the hair follicle bulge region.
25. K6 & K16
 These keratins are expressed in epidermis of
plantar glabrous skin, hair follicle outer root
sheath and companion layer.
 They are the constitutive components of nail
 Mutations in K6/K16 give rise to pachyonychia
congenita type I.
 These keratins are inducible upon stress, injury or
 K17 is a basal/myoepithelial cell keratin.
 It is expressed in myoepithelial cells of complex
tissues, including various glands (sweat glands),
respiratory epithelium and urothelium.
 It is a prominent component of the suprabasal cell
layers of outer follicular root sheath.
27.  After skin injury, K17 is switched on in
regenerating and migrating epidermal keratinocytes
upon wound healing.
 K17 mutations have been identified in
pachyonychia congenita type II and steatocystoma
 Like K6/K16, these keratins are also inducible
upon stress, injury or inflammation.
28. K1 & K10
 In the epidermis, the transition of keratinocytes
from basal cell layer to suprabasal spinous cell
layer is characterised by a profound change in
 This involves a switch from expression of basal
cell keratins ( K5, K14, K15 ) to suprabasal epidermal
keratins, k1 and subsequently K10.
29.  Keratin filaments composed of K1/K10 pair form
particularly dense bundles which are so
characteristic of suprabasal epidermal
 This imparts mechanical integrity to the cells and
the whole epidermis.
 K10 specifically inhibits proliferation and cell cycle
progression of keratinocytes.
 Loss of K10 leads to increased keratinocyte
30.  Mutations in K1 and K10 are associated with
blistering disorder – bullous congenital icthyosiform
 Therefore, K1 and K10 are regarded as
keratinization markers of keratinocytes.
 K9 is a highly specific keratin of terminally
differentiating keratinocytes of palmoplantar
 Mutations in K9 gene are associated with skin
disorder – epidermolytic palmoplantar keratoderma.
 Keratin specific for advanced terminal
differentiation process of epidermal keratinocytes.
 It is expressed in the uppermost epidermal layers -
upper stratum spinosum, stratum granulosum.
 Mutations in K2 are associated with icthyosis
bullosa of Siemens.
33. K3 & K12
 K3/ K12 are the keratin pair of the corneal
 They are expressed in all corneal epithelial cell
 Mutations in these keratins give rise to
Meesmann’s corneal dystrophy.
34. K4 & K13
 They are a highly characteristic keratin pair
indicating mucosal path of keratin differentiation.
 They are expressed in the entire suprabasal
compartment of mucosal stratified squamous
 They are absent in the epidermis and adnexa.
 Mutations in these keratins cause the disorder
white sponge nevus of Cannon.
 K76 is a highly specific keratin expressed in
suprabasal cell layers of oral masticatory
 They are found in the slightly orthokeratinized
stratified squamous epithelium lining the gingiva
and hard palate.
 Highly specific keratin restricted to the luminal
cells of eccrine sweat glands.
 Used as an eccrine duct marker.
37. Hair follicle specific keratins
 K25 - 28, K71 - 75
 These keratins are specifically expressed in the
companion layer, Henle’s layer, Huxley’s layer and
inner root sheath of the hair follicle.
 Mutations in K75 predispose to the hair disorder
38. Keratins of Hair Fiber
 K31 - 40, K81 - 86.
 These keartins are expressed within the cuticle
and the cortex of the hair follicle.
 Mutations in some of these keratins leads to
disorders like monilethrix and ectodermal dysplasia
of hair and nail type.
39. Keratins with unknown expression
 K23, K24, K78, K79, K80
 These five, very different keratins complete the
family of human keratin proteins.
 But their expression patterns and functions are