Regulates high density lipoprotein (HDL) cholesterol metabolism by promoting the ubiquitination and degradation of the oxysterols receptors LXR (NR1H2 and NR1H3). High expression in lung and spleen. Low lower expression in liver and small intestine. Weak expression in heart, brain, kidney, adipose, and adrenal gland. Chow-fed deficient mice display increased HDL-cholesterol level, accompanied by increased ABCA1 and MYLIP expression, increased oxysterols receptors LXR (NR1H3 AND NR1H2) protein level without change in NR1H2/3 mRNA levels. Many NR1H2/3 targets are up-regulated, including ABCG5/8, SCD1, ELOVL5, INSIG2 and LPCAT3. Deficiency of TTC39B reduced processing of SREBP1 a pivotal regulator of lipogenesis. When fed with a high-fat/high-cholesterol/bile-salt diet during 20 weeks, used as a model of steatohepatitis resembling human non-alcoholic steatohepatitis, mice show increased HDL cholesterol and APOA1 levels, reduced VLDL (very low density lipoprotein), and reduced mortality compared with wild-type. The livers of deficient mice shown diminished hepatic triglyceride and cholesteryl ester accumulation, fewer inflammatory foci consisting of neutrophils and lymphocytes, less hepatocellular ballooning degeneration and less hepatocyte proliferation compared to control. Knockout mice lacking both TTC39B and LDLR, fed a Western diet for 20 weeks, exhibit a reduction in LDL-cholesterol, but plasma triglyceride levels are not different. Atherosclerotic lesion area of the aorta are reduced compared to LDLR single knockout mice. Belongs to the TTC39 family.