ZNF750 is a zinc finger transcription factor that serves as a master regulator of epidermal differentiation and homeostasis. In the epidermis, ZNF750 is expressed exclusively in differentiated keratinocytes and functions downstream of p63/TP63 to activate late differentiation genes, including KLF4 1. A critical function of ZNF750 involves suppressing inflammatory responses by recruiting the histone demethylase KDM1A to silence pattern recognition receptor genes (TLR3, IFIH1, DDX58) in differentiated keratinocytes 1. Loss of ZNF750 results in excessive inflammation resembling psoriatic skin 1. Additionally, ZNF750 regulates epidermal lipid homeostasis by directly controlling expression of enzymes involved in ceramide biosynthesis, thereby maintaining cutaneous barrier function 2. Beyond skin, ZNF750 functions as a tumor suppressor in esophageal squamous cell carcinoma (ESCC) by directly repressing SNAI1 promoter activity and inhibiting epithelial-mesenchymal transition 3. ZNF750 mutations are frequently observed in ESCC and correlate with poor prognosis 3. Germline ZNF750 mutations cause seborrhea-like dermatitis with psoriasiform elements, highlighting its essential role in skin health 2. ZNF750 also positively regulates GPR37 expression, indirectly contributing to ESCC radiosensitivity 4.