APOA4 (apolipoprotein A4) is a major structural component of chylomicrons and high-density lipoproteins (HDL) located on chromosome 11 1. Functionally, APOA4 plays critical roles in lipid metabolism by activating lipoprotein lipase in conjunction with ApoC-II and serving as a potent activator of LCAT, while also participating in cholesterol transfer and HDL particle remodeling. The gene exhibits anti-inflammatory properties through transcriptional induction of SERPINA3 via nuclear receptors NR4A1 and NR1D1 2. Genetically, APOA4 is part of a tandemly organized cluster with APOA1 and APOC3 on chromosome 11, showing evolutionary conservation with distinct intron organization 1. Polymorphisms in the APOA4-APOA5-ZPR1-BUD13 gene cluster associate with lipid metabolism, with interactions observed between genetic variants and environmental factors like sleep duration affecting triglyceride and HDL-cholesterol changes 34. Clinically, pathogenic APOA4 mutations cause autosomal dominant tubulointerstitial kidney disease through medullary amyloidosis. Missense variants (p.L66V and p.D33N) expand amyloidogenic hotspots, with affected individuals showing CKD, elevated plasma ApoA4 concentrations, and a mean age for kidney failure of 64.5 years 5. Age-related TFEB downregulation in proximal tubules predisposes to APOA4 amyloidosis through impaired autophagy-lysosomal function and mitochondrial dysfunction 6.