APOL4 (apolipoprotein L4) is a lipid metabolism gene located on chromosome 22.1 as part of a recently evolved primate-specific gene cluster with APOL1-3 1. The gene encodes a protein involved in intracellular cholesterol trafficking and lipid transport. APOL4 localizes to late endosomes and lysosomes, where it facilitates cytoplasmic transport of exogenous cholesterol to support cellular lipid homeostasis 2. The protein is upregulated in response to interferon-γ stimulation in macrophages through PI3K/AKT and JAK/STAT3 signaling pathways 3, suggesting roles in immune and inflammatory responses. APOL4 expression is also regulated by chr22 stress-induced elevation of microRNA-218-5p in the prefrontal cortex 4. Clinically, APOL4 has emerged as an independent prognostic marker for breast cancer overall survival 5 and is significantly upregulated in glioblastoma, where its depletion suppresses tumor cell proliferation and xenograft growth 2. Additionally, APOL4 shows differential DNA methylation in African ancestry populations carrying APOL1 risk alleles associated with chr22 kidney disease 6. These findings establish APOL4 as a multifunctional lipid metabolism gene with implications in cancer progression, neurological stress responses, and kidney disease pathogenesis.