Chp1, also known as calcineurin B homologous protein 1 or calcineurin-like EF-hand protein 1, plays diverse and crucial roles in various biological processes. It is involved in pathways such as glycerolipid synthesis, protein folding at the ribosome, and regulation of ion transporters, which are essential for cell survival, proliferation, and maintaining cellular homeostasis. Genetic models, like KO/CKO mouse models, are valuable in studying its functions [2-5, 9, 10].

In KO/CKO mouse models and other loss-of-function experiments, loss of Chp1 in mammalian cells and invertebrates severely reduces fatty acid incorporation and storage as it regulates glycerolipid synthesis by activating GPAT4 [1]. In spinal muscular atrophy (SMA) mouse models, elevated CHP1 levels were found, and CHP1 reduction restored impaired axonal growth, improved disease hallmarks, and prolonged survival, suggesting it as a potential therapeutic target [2]. In Chp1 mutant (vacillator) mice, PLS3 overexpression delayed the ataxic phenotype, indicating PLS3 as a cross-disease modifier for Chp1-causing ataxia [3]. Also, Chp1-deficient Purkinje cells showed reduced membrane localization of NHE1 and axon degeneration, emphasizing the importance of the CHP1-NHE1 interaction in axon homeostasis [4]. A biallelic CHP1 mutation in humans and Chp1 deficiency in zebrafish led to ataxia-related phenotypes, revealing CHP1 as a novel ataxia-causative gene [5].

In conclusion, Chp1 is essential for processes like glycerolipid metabolism, protein folding of eEF1A, and maintaining axon homeostasis. Studies using KO/CKO mouse models and other in vivo models have been instrumental in uncovering its role in diseases such as SMA and ataxia, providing insights into potential therapeutic strategies for these conditions.