KRTAP1-1 (keratin-associated protein 1-1) is a structural protein essential for hair shaft formation. In the hair cortex, KRTAP1-1 functions as part of an interfilamentous matrix that embeds hair keratin intermediate filaments, providing rigidity and resistance to the hair shaft through extensive disulfide bond cross-linking with cysteine-rich hair keratins [UniProt annotation]. The protein is expressed in differentiated portions of the hair follicle cortex as a member of the high-sulfur keratin-associated protein 1 family 1. Beyond its classical hair structural role, emerging evidence suggests unexpected functions. A loss-of-function variant (rs3213755) in KRTAP1-1 was significantly associated with remission following SSRI antidepressant treatment in major depressive disorder patients (p=0.00269, OR 1.75 in replication cohort of 553 patients), with expression levels correlating to genotype 2. Additionally, the KRTAP_region_1 (containing KRTAP1-1 genes) on chromosome 17-21 represents a genomic fragility hotspot more prone to DNA breaks than common fragile sites, frequently demarcating ERBB2 amplicons in breast tumors and triggering cancer-associated genome rearrangements 3. These findings suggest KRTAP1-1 has roles extending beyond keratin binding, though mechanisms remain unclear and warrant further investigation.