SDR42E1 encodes a short-chain dehydrogenase/reductase enzyme with NAD(P)H-dependent oxidoreductase activity 1. The gene functions as a key modulator of vitamin D homeostasis and sterol metabolism. SDR42E1 demonstrates strong binding affinity for vitamin D3 and its precursors (7-dehydrocholesterol and 8-dehydrocholesterol) 2, and is highly expressed in skin keratinocytes where it regulates the steroid biosynthesis pathway 3. SDR42E1 deficiency disrupts this pathway, causing accumulation of 7-dehydrocholesterol precursor and reduced vitamin D3 production 3. Functionally, loss of SDR42E1 significantly reduces cell viability and dysregulates sterol absorption genes, including upregulation of LRP1B and ABCC2 and downregulation of WNT16 1. Clinically, SDR42E1 mutations associate with vitamin D deficiency and altered steroid hormone synthesis 4. A nonsense variant in SDR42E1 linked to vitamin D deficiency has been identified 1, and the rs11542462 SNP represents a genetic regulator of vitamin D status 3. Additionally, SDR42E1 dysregulation occurs in ectopic pregnancy 5 and congenital heart defects 6, suggesting broader roles in developmental and reproductive pathology. SDR42E1 represents a promising therapeutic target for precision medicine approaches to vitamin D deficiency.