TCHH (trichohyalin) is an intermediate filament-associated protein that plays a critical role in hair and skin barrier formation. It associates with keratin intermediate filaments in inner root sheath cells and the epidermal granular layer, becoming cross-linked through isodipeptide bonds during terminal differentiation 1. TCHH belongs to the S100 fused-type protein family alongside filaggrin and hornerin, contributing to cornified envelope organization and the cell envelope scaffold structure 1. The protein exhibits calcium-dependent postsynthetic processing during epidermal differentiation 2. At the molecular level, dermal adipose tissue-derived HGF upregulates TCHH expression in hair matrix keratinocytes through Wnt/Ξ²-catenin signaling activation, promoting hair growth and pigmentation 2. TCHH expression is downregulated in atopic dermatitis skin models stimulated with IL-4 and IL-13 1. Clinically, TCHH variants are associated with uncombable hair syndrome (UHS), a rare genetic hair shaft disorder; only 2 of 80 genetically characterized UHS cases carried TCHH mutations, with most attributable to PADI3 variants 3. Additionally, TCHH polymorphisms (rs11803731) significantly predict hair morphology in Europeans, with specific genotype combinations showing >80% probability of straight hair 4. TCHH methylation in circulating free DNA serves as a noninvasive biomarker for liver metastasis in colorectal cancer 5, suggesting broader pathological relevance beyond dermatology.