COL6A5 encodes collagen type VI alpha 5 chain, a component of the extracellular matrix that functions as a cell-binding protein conferring tensile strength 1. While most collagen VI-related mutations involve COL6A1, COL6A2, and COL6A3, COL6A5 has emerged as a functionally important variant with tissue-specific roles. In skin, COL6A5+ fibroblasts represent a novel inflammatory subpopulation unique to atopic dermatitis lesions that secretes chemokines (CCL2, CCL19) to recruit immune cells, particularly CCR7+ dendritic cells, suggesting COL6A5 participates in immune cell crosstalk and type 2 inflammation 23. Functionally, COL6A5 mutations have been identified in familial neuropathic chr3 itch associated with small fiber neuropathy, with both nonsense and missense variants causing reduced expression and disorganized protein localization in patient skin 4. COL6A5 variants are also enriched in Chiari Malformation Type 1, particularly in connective tissue disorder-associated cases, with 26% of CM-1 patients harboring COL6A5 variants 5. Additionally, COL6A5 variants control bone mineral density variation in both mouse and human populations 6, and stabilized COL6A5 promotes gastric cancer metastasis through protein stabilization mechanisms 7. These findings establish COL6A5 as functionally distinct from other collagen VI chains with roles in immune regulation, neuropathic disease, skeletal development, and cancer progression.