TMEM79 (transmembrane protein 79) is a multi-span transmembrane protein that functions as a critical regulator of skin barrier integrity and immune homeostasis. Primarily, TMEM79 contributes to epidermal barrier function through its involvement in the lamellar granule secretory system and stratum corneum formation 1. Mechanistically, TMEM79 operates through multiple pathways: it negatively regulates Wnt/Frizzled signaling by suppressing USP8-mediated deubiquitination of Frizzled receptors, promoting their degradation 2, and acts as a negative regulator of TRPV3 thermoreceptors by promoting lysosomal degradation and modulating their cellular translocation 3. Additionally, TMEM79 confers protection from oxidative stress accumulation in keratinocytes and sensory neurons 4. Clinically, TMEM79 mutations have significant disease relevance. Loss of keratinocytic TMEM79 is sufficient to trigger atopic dermatitis through mast cell accumulation and histaminergic itch pathways 4, and a missense SNP (rs6684514) in human TMEM79 shows association with AD susceptibility 1. Beyond dermatology, TMEM79 demonstrates broader pathophysiological roles: it ameliorates cerebral ischemia/reperfusion injury via the Nrf2/NLRP3 pathway 5, and elevated TMEM79 expression correlates with prognostic outcomes in hepatocellular carcinoma and prostate cancer through modulation of immune infiltration and drug sensitivity 67. These findings establish TMEM79 as a multifunctional regulator relevant to inflammatory, neurological, and malignant diseases.