TTC39B encodes a tetratricopeptide repeat domain protein that serves as a critical regulator of lipid metabolism and cellular homeostasis. The protein functions as a scaffolding molecule that promotes the ubiquitination and degradation of liver X receptors (LXRα and LXRβ), key transcription factors controlling cholesterol homeostasis 1. TTC39B deficiency stabilizes LXR proteins, leading to increased HDL cholesterol levels and enhanced cholesterol efflux through upregulation of ABCA1 expression 1. The protein also destabilizes the retinoblastoma (pRb) tumor suppressor protein, promoting hepatic lipogenesis in a sex-specific manner, with stronger effects observed in females 2. Additionally, TTC39B interacts with VAPB and SCAP proteins to regulate lipid synthesis pathways 2. Genome-wide association studies have identified TTC39B variants as significantly associated with plasma lipid levels and cardiovascular disease risk 3. Clinical relevance extends beyond lipid disorders, as variants in TTC39B are associated with endometriosis 4 and cholelithiasis 5. Interestingly, TTC39B also functions in ketocarotenoid biosynthesis, contributing to red coloration in vertebrates 6. These diverse functions establish TTC39B as a multifunctional protein with significant implications for metabolic diseases and therapeutic intervention strategies.