NCKAP1, also known as Nck-associated protein 1, is crucial for cytoskeletal functions, regulating neuronal cytoskeletal dynamics and essential for neuronal differentiation in the developing brain [1,4]. It is part of the pentameric cytoskeletal SCAR/WAVE complex, a major downstream target of RAC1, and is involved in pathways like ribosomal signaling, oxidative phosphorylation, TGF-β, and EMT-related signaling [2,3].

In neurodevelopment, mouse in utero electroporation experiments (a form of in vivo study) show that Nckap1 loss of function promotes neuronal migration during early cortical development, suggesting its role in neurodevelopmental delay/autism [1]. In melanoma mouse models, targeted deletion of Nckap1 in the melanocyte lineage delayed tumor onset and progression, highlighting its role in cell-cycle progression and tumor tissue integrity [6]. In renal cell carcinoma, overexpression of NCKAP1 in cell lines reduced proliferation, invasion, migration capacity in vitro and inhibited tumor growth in vivo, and it may suppress cancer cell growth via the PI3K/AKT/mTOR signaling pathway [2,3,5].

In conclusion, NCKAP1 plays essential roles in neuronal development and cancer-related processes. The use of gene knockout (KO) or conditional knockout (CKO) mouse models in functional studies has been instrumental in revealing its functions in neurodevelopmental disorders and cancer, providing valuable insights into the underlying mechanisms and potential therapeutic targets.