VRK1 is a nuclear serine/threonine kinase regulating multiple cellular processes critical for neuronal function and genomic stability. Primary function: VRK1 controls cell cycle progression, chr14 organization, and DNA damage response through phosphorylation of histone H3 at Thr3/Thr4 and histone H2AX, facilitating G0 exit and G2/M transition 1. Mechanism: VRK1 phosphorylates key substrates including p53 at Thr18 (preventing MDM2 interaction), BANF1 (disrupting DNA binding), KAT5 (promoting histone acetyltransferase activity), and COIL (regulating Cajal body assembly) 2. It organizes Cajal bodies essential for RNP complex assembly and neuronal migration 1. Disease relevance: Recessive VRK1 variants cause distal hereditary motor neuropathy, amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, and spinal muscular atrophy, primarily through impaired Cajal body stability and DNA damage responses 31. Clinical significance: VRK1 is overexpressed in nervous system tumors (glioblastoma, neuroblastoma), enabling therapeutic targeting via synthetic lethality when VRK2 is methylated 45. VRK1 inhibition represents a promising strategy in VRK2-deficient cancers.