Cdk5r1, also known as cyclin-dependent kinase 5 regulatory subunit 1, encodes for p35, the main activator of Cyclin-dependent kinase 5 (CDK5). The active p35/CDK5 complex is crucial for central nervous system development, neuronal migration, and is involved in numerous aspects of brain function [4,7]. It also has implications in various biological processes and diseases through associated pathways like notch signaling pathway [1]. Genetic models are valuable for studying Cdk5r1 function.

In hepatocellular carcinoma (HCC), high Cdk5r1 expression is associated with poor prognosis, including overall survival, disease-specific survival, disease-free interval, and progression-free interval. It is significantly related to tumor status, new tumor event, clinical stage, and topography [1]. In Schwann cells, overexpression of Cdk5r1 promotes proliferation, migration, and production of neurotrophic factors, and inhibits apoptosis via the CDK5/BDNF/TrkB pathway after sciatic nerve injury, suggesting its role in nerve injury recovery [2]. In β-cells, overexpression of Cdk5r1 can induce primary β-cell proliferation while maintaining glucose-stimulated insulin secretion and confers protection against apoptosis induced by some agents [3]. In Ewing's sarcoma cells, miR-152 suppresses cell proliferation by targeting Cdk5r1, indicating its role in tumorigenesis [5]. In colorectal and breast malignancies, elevated Cdk5r1 expression is associated with poor prognosis, proliferation, and drug resistance [6].

In conclusion, Cdk5r1 plays essential roles in processes such as nervous system development, nerve injury recovery, β-cell proliferation, and is implicated in multiple diseases including various cancers. Model-based research, especially potentially through gene knockout (KO) or conditional knockout (CKO) mouse models in the future, has the potential to further clarify its functions in these disease areas.