HEPHL1 (hephaestin like 1) is a copper-binding glycoprotein with ferroxidase activity that oxidizes ferrous iron (Fe2+) to ferric iron (Fe3+) without generating reactive oxygen species 1. The protein localizes to the plasma membrane and plays a role in regulating intracellular iron homeostasis 1. HEPHL1 belongs to a family of multicopper ferroxidases alongside ceruloplasmin and hephaestin, which facilitate iron redox chemistry critical for biological processes 1. Biallelic loss-of-function mutations in HEPHL1 cause an autosomal recessive disorder characterized by abnormal hair phenotypes, including pili torti and trichorrhexis nodosa, alongside cognitive dysfunction 1. Affected individuals' fibroblasts accumulate intracellular iron and show reduced lysyl oxidase activity, a copper-dependent enzyme 1. Animal models similarly exhibit curly whisker phenotypes 1. A nonsense variant (p.Lys562*) in cattle causes breed-specific congenital hypotrichosis 2, demonstrating that HEPHL1 dysfunction impairs hair growth across species. Beyond hair disorders, HEPHL1 variants associate with colorectal adenoma risk in a diet-dependent manner 3, and genome-wide analyses identify HEPHL1 as a causal protein biomarker for vitiligo 4. HEPHL1 also appears as a hub gene in COVID-19 pathogenesis and has been identified in cancer-related gene networks 56.