NCKAP1, also known as Nck-associated protein 1, is crucial for cytoskeletal functions and various cellular activities [2,3,4]. It regulates the actin cytoskeleton and is part of the WAVE2 complex, which is associated with the regulation of small GTPase-mediated signal transduction [2,5]. NCKAP1 is essential for neuronal cytoskeletal dynamics and neuronal differentiation in the developing brain [1].

In a mouse model of melanoma driven by BRAFV600E;PTEN loss, targeted deletion of Nckap1 in the melanocyte lineage delayed tumor onset and progression, highlighting its role in cell-cycle progression and maintaining tumor tissue integrity [6]. In utero electroporation experiments in mice showed that Nckap1 loss of function promotes neuronal migration during early cortical development, suggesting its role in neurodevelopmental delay/autism [1].

In conclusion, NCKAP1 plays essential roles in multiple biological processes. Its function in regulating cytoskeletal dynamics is crucial for normal development. Mouse models, especially those with Nckap1 knockout, have revealed its significance in diseases such as melanoma and neurodevelopmental disorders, providing insights into the underlying mechanisms and potential therapeutic targets [1,6].

References:

1. Guo, Hui, Zhang, Qiumeng, Dai, Rujia, Eichler, Evan E, Xia, Kun. . NCKAP1 Disruptive Variants Lead to a Neurodevelopmental Disorder with Core Features of Autism. In American journal of human genetics, 107, 963-976. doi:10.1016/j.ajhg.2020.10.002. https://pubmed.ncbi.nlm.nih.gov/33157009/

2. Liang, Xiao, Hong, Aonan, Shen, Ruizhi, Zhu, Minmin, Tian, Weiqian. 2024. NCKAP1 as a prognostic and immunological biomarker: pan-cancer analysis and validation in renal clear cell carcinoma. In American journal of translational research, 16, 4083-4100. doi:10.62347/UKQB2042. https://pubmed.ncbi.nlm.nih.gov/39262720/

3. Chen, Jiasheng, Ge, Jianzhang, Zhang, Wancong, Zhong, Xiaoping, Tang, Shijie. 2022. NCKAP1 is a Prognostic Biomarker for Inhibition of Cell Growth in Clear Cell Renal Cell Carcinoma. In Frontiers in genetics, 13, 764957. doi:10.3389/fgene.2022.764957. https://pubmed.ncbi.nlm.nih.gov/35957696/

4. Zhang, Xin, Ye, Jianqing, Sun, Lixiang, Bao, Juan, Wang, Jin. 2025. NCKAP1 Inhibits the Progression of Renal Carcinoma via Modulating Immune Responses and the PI3K/AKT/mTOR Signaling Pathway. In International journal of molecular sciences, 26, . doi:10.3390/ijms26062813. https://pubmed.ncbi.nlm.nih.gov/40141455/

5. Edwards, Jonathan J, Rouillard, Andrew D, Fernandez, Nicolas F, Ma'ayan, Avi, Gelb, Bruce D. 2020. Systems Analysis Implicates WAVE2 Complex in the Pathogenesis of Developmental Left-Sided Obstructive Heart Defects. In JACC. Basic to translational science, 5, 376-386. doi:10.1016/j.jacbts.2020.01.012. https://pubmed.ncbi.nlm.nih.gov/32368696/

6. Swaminathan, Karthic, Campbell, Andrew, Papalazarou, Vassilis, Sansom, Owen J, Machesky, Laura M. 2020. The RAC1 Target NCKAP1 Plays a Crucial Role in the Progression of Braf;Pten-Driven Melanoma in Mice. In The Journal of investigative dermatology, 141, 628-637.e15. doi:10.1016/j.jid.2020.06.029. https://pubmed.ncbi.nlm.nih.gov/32777214/