LCE proteins

LCE proteins (LCE stands for: Late Cornified Envelope) are small cationic epidermal proteins, components of the epidermal differentiation region (EDC). The respective coding genes are localized in a gene cluster on chromosome 1q21. The LCE proteins are expressed late (late cornified envelope) in keratinocyte differentiation in the stratum granulosum/stratum corneum as a component of the cornified envelope (CE) (Niehues H et al. 2023).

The LCE proteins stabilize the epidermal barrier, the mechanical integrity. They also prove to be important factors in antimicrobial defense.

The "cornified envelope" is a membrane-like, 15 nm thick, dense and very poorly soluble structure on the inner side of the corneocyte cell membrane. They thus form a protective barrier against environmental factors that is difficult to penetrate. The "cornified envelope" is composed of numerous proteins. These include: filaggrins, involucrin, loricrin, the small proline rich proteins (SPR), repetin, etc. The genes of these proteins are all located in the cluster of the epidermal differentiation complex (EDC), which is located in chromosome 1q21. The CE develops during keratinization, which can be described as a special form of controlled, physiological apoptosis.

There are 18 known functional LCE genes, which are divided into 6 subfamilies (LCE1-LCE6).

LCE1 proteins/LCE1 gene/constitutive barrier

• LCE1A protein/LCE1A gene /keratinization process
• LCE1B protein /healthy skin
• LCE1C protein /terminal differentiation
• LCE1D protein /low inflammatory response
• LCE1E protein / LCE1E gene / cornification process stratum granulosum stratum corneum

• LCE2A protein/structural stability of the cornified envelope
• LCE2B protein/structural stability of the cornified envelope
• LCE2C protein/barrier protein
• LCE2D protein/keratin-associated

LCE1A-F and LCE2A-D can be described as constitutive LECs. They are permanently expressed in normal skin and ensure the mechanical stability of the epidermis.

LCE3 proteins/inducible by inflammation

• LCE3A protein/ LCE3A gene
• LCE3B protein/ LCE3B gene /wound response/
• LCE3C protein/ LCE3C gene /psoriasis-associated/
• LCE3D protein/barrier repair
• LCE3E protein/ antimicrobial

The LCE3-3E can be described as stress or inflammatory proteins. They are strongly inducible in the case of barrier disorders, epithelial injuries, after stimulation by various cytokines, for example in the case of Cytokines, for example in psoriasis. Susceptibility genes within the late cornified envelope (LCE) gene cluster have been identified for psoriasis (Ps) and psoriatic arthritis (PsA), in particular the gene of cluster 3 (LCE3). The deletion of LCE3B and LCE3C (LCE3C_LCE3B-del) are significantly associated with these two diseases. Gene-gene interactions between LCE3 genes and other genes are also associated with Ps and PsA. LCE3 genes also have a pleiotropic effect on some autoimmune diseases, such as rheumatoid arthritis, atopic dermatitis and systemic lupus erythematosus (Shen C et al. 2015; Docampo E et al. 2010; de Cid R et al. 2009).

LCE4 protein/LCE4A gene/late differentiation protein

LCE5 protein/LCE5A gene/strongly hydrophobic protein

LCE6 protein/LCE6A gene/lowly expressed, function?

The special forms LCE4- LCE6 are only slightly expressed. They are assumed to be structural elements in the CE cross-linking.

1. Bowcock AM et al. (2004) The genetics of psoriasis, psoriatic arthritis and atopic dermatitis. Hum. Mol. Genet 13(Spec No 1):R43-55. -
2. de Cid R et al. (2009) Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis. Nat Genet 41:211-215.
3. Docampo E et al. (2010) Deletion of the late cornified envelope genes, LCE3C and LCE3B, is associated with rheumatoid arthritis. Arthritis Rheum 62:1246-1251.
4. Niehues H et al. (2023) CYSRT1: An Antimicrobial Epidermal Protein that Can Interact with Late Cornified Envelope Proteins. J Invest Dermatol 143:1498-1508.e7.
5. Shen C et al. (2015) Association of the late cornified envelope-3 genes with psoriasis and psoriatic arthritis: a systematic review. J Genet Genomics 42:49-56
6. Zhang XJ et al. (2009) Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. Nat Genet 41:205-210.