CDKL1 (cyclin-dependent kinase-like 1) is a serine-threonine protein kinase with pleiotropic roles in neurodevelopment, ciliary biology, and cancer regulation. Primary Function: CDKL1 encodes a kinase involved in multiple cellular processes. It associates with intraflagellar transport machinery and controls ciliary proximal segment length, a function conserved from C. elegans to mammals 1. Mechanism: CDKL1 localizes to cilia and nucleoplasm, phosphorylating target proteins to regulate cell cycle progression and protein signaling. In lung cancer, CDKL1 interacts with transcription factor YBX1 to suppress PD-L1 expression, enhancing anti-tumor immunity 2. Disease Relevance: De novo CDKL1 variants cause neurodevelopmental disorders including global developmental delay, intellectual disability, and childhood-onset epilepsy, acting as dominant-negative alleles 3. CDKL1 variants impair ciliary formation and predispose to thoracic aortic aneurysm and dissection through disrupted vascular smooth muscle cell function 4. CDKL1 is upregulated in melanoma, neuroblastoma, and oral squamous cell carcinoma; knockdown suppresses proliferation and chemoresistance 567. CDKL1 emerges as a lactate metabolism-related biomarker in Alzheimer's disease 8. Clinical Significance: CDKL1 represents a potential therapeutic target for cancer treatment, particularly when combined with immunotherapy and radiotherapy in lung cancer.