PI4K2B encodes a phosphatidylinositol 4-kinase that catalyzes the phosphorylation of phosphatidylinositol to phosphatidylinositol 4-phosphate (PI4P), contributing to the overall cellular PI4-kinase activity alongside PI4K2A and the type III PI4Ks. This activity is particularly significant at the plasma membrane, endosomal, and Golgi compartments. PI4P generation represents the first committed step toward phosphatidylinositol 4,5-bisphosphate synthesis and the second messenger inositol 1,4,5-trisphosphate, making PI4K2B involved in vesicular trafficking and signal transduction. PI4K2B has been associated with multiple neuropsychiatric and malignant phenotypes. A candidate gene study identified association with schizophrenia 1, and genome-wide association studies linked PI4K2B to cannabis use 2 and to sleep apnea with excessive daytime sleepiness through gene-by-environment interaction 3. In small cell lung cancer, increased PI4K2B expression correlated with poor overall survival in a cisplatin resistance-related prognostic model 4. Conversely, in colorectal cancer stratified by tumor location, increased PI4K2B expression associated with improved survival in distal tumors 5. PI4K2B was also identified as an HLA class II-restricted target in graft versus leukemia reactivity against chr4 myeloid leukemia 6. These findings suggest PI4K2B has context-dependent roles in malignancy and psychiatric disease, though the mechanisms underlying these associations require further investigation.