CHKA (choline kinase alpha) is a multifunctional enzyme with dual roles in lipid metabolism. Canonically, it catalyzes the first committed step of the CDP-choline pathway for phosphatidylcholine biosynthesis 1. Under metabolic stress, CHKA undergoes a remarkable functional transformation: upon glucose deprivation, AMPK-mediated phosphorylation and KAT5-mediated acetylation convert dimeric CHKA into a monomeric protein kinase that phosphorylates lipid droplet proteins PLIN2 and PLIN3, promoting their autophagy-mediated degradation and lipid droplet lipolysis 2. Beyond lipid catabolism, CHKA regulates metabolic pathways critical for disease pathogenesis. In hepatocellular carcinoma development, CHKA activation occurs downstream of EGF-EGFR signaling to promote oncogenic transcription 3. In diabetes-associated microvascular dysfunction, CHKA-mediated angiogenesis proceeds through NAD+-SIRT1-Notch signaling 4. CHKA also couples to PI3K-AKT pathway activation in colorectal cancer proliferation 5. Biallelic CHKA variants cause neurodevelopmental disorder with epilepsy, microcephaly, and intellectual disability by impairing phospholipid synthesis and elevating mitochondrial reactive oxygen species 1. These findings establish CHKA as a central metabolic integrator linking nutrient availability, lipid homeostasis, and disease progression across multiple pathological contexts.