SEC16B is a scaffold protein localized to endoplasmic reticulum exit sites (ERES) that plays specialized roles in intracellular trafficking. Functionally, SEC16B is required for COPII vesicle assembly and organization of transitional ER, facilitating cargo export from the ER to the Golgi apparatus 1. SEC16B also regulates peroxisomal biogenesis by controlling transport of PEX3 and PEX16 from the ER to peroxisomes 2. Unlike the broader SEC16A isoform, SEC16B appears to have non-redundant, specialized functions 1. SEC16B expression is regulated by ER stress through unfolded protein response elements and ATF4-responsive sequences 3. Disease relevance is substantial across multiple conditions. Genome-wide association studies consistently link SEC16B polymorphisms (rs543874, rs10913469, rs633715) to increased obesity and BMI risk across diverse ethnic populations 456. Mechanistically, intestinal SEC16B deficiency impairs chylomicron secretion and apoB lipidation, reducing postprandial triglyceride output 7. Clinically, homozygous SEC16B mutations cause osteogenesis imperfecta through collagen trafficking defects, ER accumulation, and enhanced ER stress 8. Additionally, SEC16B variants associate with female-specific susceptibility to adolescent idiopathic scoliosis 9.