Cstpp1, also known as C11ORF49, is a novel regulator of the tubulin polyglutamylase complex (TPGC). It plays a crucial role in regulating cytoskeletal organization, nuclear shape, and cilium disassembly by balancing microtubule and actin assembly [1]. This gene is associated with pathways related to cytoskeleton regulation and ciliogenesis, which are vital for normal cellular functions and development. Genetic models are valuable for studying its function.

Loss-of-function of Cstpp1 impacts the assembly and stability of the TPGC. This leads to abnormal microtubule assembly, with microtubules penetrating the nucleus, causing nuclear shape defects. It also disrupts cytoplasmic actin organization, interfering with the YAP/TAZ pathway and cilium disassembly. In vivo, disruption of Cstpp1-TPGC results in developmental defects [1]. Additionally, in human sperm subpopulations, Cstpp1 is downregulated in low-motility sperm, suggesting its potential as a biomarker for fertility [2].

In summary, Cstpp1 is essential for maintaining proper cytoskeletal and nuclear architecture, cilium disassembly, and potentially fertility. Model-based research, especially loss-of-function studies, has revealed its significance in these biological processes and in developmental and fertility-related areas.

References:

1. Wang, Lei, Paudyal, Sharad C, Kang, Yuchen, Sánchez, Irma, Dynlacht, Brian D. 2021. Regulators of tubulin polyglutamylation control nuclear shape and cilium disassembly by balancing microtubule and actin assembly. In Cell research, 32, 190-209. doi:10.1038/s41422-021-00584-9. https://pubmed.ncbi.nlm.nih.gov/34782749/

2. Caballero-Campo, Pedro, Lira-Albarrán, Saúl, Amaral, Alexandra, Rinaudo, Paolo, Chirinos, Mayel. 2025. Integrative Molecular and Functional Analysis of Human Sperm Subpopulations to Identify New Biomarkers of Fertilization Potential. In Archives of medical research, 56, 103210. doi:10.1016/j.arcmed.2025.103210. https://pubmed.ncbi.nlm.nih.gov/40168948/