Protein S1-A3, also known as Protein S-1E, S1 calcium-binding protein A3, S1A3 and S1E, is a member of the S-1 family. S1A3 / S1E contains 2EF-hand domains. S1A3 / S1E is highly expressed in the differentiating cuticular cells within the hair follicle and organized into mature hair cuticles. High concentrations of S1A3 homotetramer might provide the millimolar level of Ca2+ required for hair cuticular barrier formation. S1A3 / S1E is a unique member of the Ca2+-binding S1 protein family with the highest cysteine content and affinity for Zn2+. S1A3 / S1E binds both calcium and zinc. S1A3 / S1E probably binds 2 zinc ions per molecule. It may be involved in calcium-dependent cuticle cell differentiation and hair shaft formation. S1A3 plays an important role in calcium-dependent processes leading to hair shaft formation. S1A3 / S1E is a unique protein among all members of the calcium-binding S1 family, is specifically expressed at the inner endocuticle of human hair fibers. Upon hair damage, S1A3 / S1E is released from hair fibers and possibly destabilizes the hair tissue architecture.