FITM2 (fat storage inducing transmembrane protein 2) is an endoplasmic reticulum (ER) integral membrane protein that functions as a fatty acyl-CoA diphosphatase, hydrolyzing fatty acyl-CoA substrates to yield acyl-4'-phosphopantetheine and adenosine 3',5'-bisphosphate 1. The protein preferentially processes unsaturated long-chain acyl-CoA substrates and plays a crucial role in lipid droplet biogenesis and ER homeostasis 1. FITM2 is essential for proper VLDL assembly in hepatocytes, as deficiency results in secretion of triglyceride-depleted VLDL particles and accumulation of triglycerides in the ER, leading to ER stress 2. The protein contributes to lipid partitioning between cytosolic lipid droplets and VLDL particles, particularly when triglyceride synthesis is stimulated 2. FITM2 also functions in cancer cell immune evasion, being required for maintaining cell fitness after interferon-γ exposure 3. Homozygous loss-of-function mutations cause Siddiqi syndrome, characterized by deafness, dystonia, motor regression, and neuropsychiatric symptoms 45. Hypomorphic mutations can cause hereditary spastic paraplegia, expanding the clinical spectrum associated with FITM2 deficiency 6. The protein's expression is regulated by peroxisome proliferator-activated receptors (PPARs), linking lipid uptake to storage capacity regulation 7.