Pcyt1a, encoding the alpha isoform of the phosphate cytidylyltransferase 1 choline enzyme, is the rate-limiting enzyme responsible for phosphatidylcholine (PC) de novo synthesis via the Kennedy pathway [5]. Phosphatidylcholine is a major phospholipid in eukaryotic membranes, and thus Pcyt1a is crucial for maintaining membrane integrity and function [4].

In a retina-specific knockout mouse model (Pcyt1a-RKO), deletion of Pcyt1a led to retinal degenerative phenotypes such as reduced scotopic electroretinogram responses, progressive photoreceptor cell degeneration, and loss of cells in the inner nuclear layer. Proteomic and bioinformatic analyses revealed dysregulated fatty acid metabolism and activation of the ferroptosis signalling pathway. Interestingly, PCYT1A deficiency did not cause an overall reduction in PC synthesis within the retina but disrupted free fatty acid metabolism and triggered ferroptosis [1]. In Vizslas with disproportionate dwarfism, a missense variant in Pcyt1a was identified, and the skeletal changes were comparable to human patients with spondylometaphyseal dysplasia with cone-rod dystrophy caused by Pcyt1a loss-of-function variants [2]. In lung adenocarcinoma, Pcyt1A suppressed cancer cell proliferation and migration by inhibiting the mTORC1 signaling pathway, and high expression predicted longer survival of lung cancer patients [3].

In conclusion, Pcyt1a is essential for phosphatidylcholine synthesis and has far-reaching impacts on various biological processes. The Pcyt1a-RKO mouse model has been instrumental in uncovering its role in retinal diseases, while studies in other species and cell lines have illuminated its functions in skeletal development and cancer, providing valuable insights into these disease areas.