CAMKV kinase drives neuroblastoma growth and acts as a novel therapeutic target.

High-risk (HR) neuroblastoma (NB) remains a leading cause of pediatric cancer mortality, frequently driven by MYCN amplification or MYC overexpression. Despite their central role, direct pharmacological targeting of these transcription factors remains clinically challenging. Here, we identify CaM kinase-like vesicle-associated protein (CAMKV) as a MYCN/MYC-regulated effector of NB pathogenesis. Although previously classified as a nonfunctional pseudokinase, we demonstrate that CAMKV possesses intrinsic kinase activity that is essential for tumor growth. Analysis of patient datasets and primary tumors shows that elevated CAMKV expression correlates with advanced disease stage and poor overall survival. Through integrated transcriptomics, ChIP-seq, and phosphoproteomics, we establish CAMKV as a central signaling hub that coordinates metabolic and proliferative pathways. Both genetic depletion and small-molecule inhibition of CAMKV significantly impair NB cell proliferation in vitro and suppress tumor growth in vivo. Collectively, our findings establish CAMKV as a unifying therapeutic vulnerability and highlight this functional kinase as a promising target for translational development in HR NB.