Pkd2l1, also known as TRPP2 or TRPP3, is a member of the transient receptor potential family and forms ciliary ion channels. It is involved in various biological processes such as hedgehog signaling, intestinal development, and sour tasting [3]. It plays a significant role in maintaining the functionality of neurons and the spinal cord, and its dysregulation may be associated with certain neurological and spinal-related conditions. Genetic models have been crucial in understanding its functions.

In mice, loss of Pkd2l1 expression leads to ablation of primary ciliary maturation in hippocampal neurons, attenuation of neuronal high-frequency excitability, and increased seizure susceptibility and autism-like behavior, suggesting its role in regulating hippocampal excitability [1]. In zebrafish, loss of the Pkd2l1 channel nearly abolishes calcium activity and single-channel opening in cerebrospinal fluid-contacting neurons (CSF-cNs), and adult pkd2l1 mutant zebrafish develop an exaggerated spine curvature, indicating its role in mechanoception in CSF-cNs and maintenance of spine curvature [2].

In conclusion, Pkd2l1 is essential for the normal function of neurons and the spinal cord. Mouse and zebrafish models have revealed its role in regulating hippocampal excitability, which may be related to neurological disorders such as autism spectrum disorder, and in maintaining spine curvature, potentially relevant to spinal-related conditions like idiopathic scoliosis. These findings provide valuable insights into the biological functions of Pkd2l1 and its implications in disease.

References:

1. Vien, Thuy N, Ta, My C, Kimura, Louise F, Onay, Tuncer, DeCaen, Paul G. 2023. Primary cilia TRP channel regulates hippocampal excitability. In Proceedings of the National Academy of Sciences of the United States of America, 120, e2219686120. doi:10.1073/pnas.2219686120. https://pubmed.ncbi.nlm.nih.gov/37216541/

2. Sternberg, Jenna R, Prendergast, Andrew E, Brosse, Lucie, Delmas, Patrick, Wyart, Claire. 2018. Pkd2l1 is required for mechanoception in cerebrospinal fluid-contacting neurons and maintenance of spine curvature. In Nature communications, 9, 3804. doi:10.1038/s41467-018-06225-x. https://pubmed.ncbi.nlm.nih.gov/30228263/

3. Zheng, Wang, Hussein, Shaimaa, Yang, JungWoo, Tang, Jingfeng, Chen, Xing-Zhen. 2015. A novel PKD2L1 C-terminal domain critical for trimerization and channel function. In Scientific reports, 5, 9460. doi:10.1038/srep09460. https://pubmed.ncbi.nlm.nih.gov/25820328/