Chp1, also known as calcineurin B homologous protein 1, serves multiple crucial functions. It is involved in cotranslational protein folding, regulating glycerolipid synthesis, and is an obligate binding partner for transporters like NHE1 and NHE3, influencing their biosynthetic maturation, cell surface expression, and pH-sensitivity. It is also associated with pathways related to endocytosis and neurodegenerative disease-related processes [1,2,3,6]. Genetic models such as KO/CKO mouse models play a significant role in studying its functions.

In Chp1-deficient mice, there are various pathological manifestations. In spinal muscular atrophy (SMA) mouse models, elevated CHP1 levels were found, and CHP1 down-regulation restored impaired axonal growth. Combining CHP1 reduction with low-dose SMN antisense oligonucleotide further prolonged the survival of severely-affected SMA mice and ameliorated disease hallmarks [4]. In Chp1 mutant (vacillator) mice, overexpression of PLS3, which interacts with CHP1, delayed the ataxic phenotype at an early stage and ameliorated axon hypertrophy in Purkinje neurons [5]. Also, in Chp1-deficient zebrafish, movement defects, cerebellar hypoplasia, and motor axon abnormalities were observed, resembling the conditions in affected human individuals [7].

In conclusion, Chp1 is essential for protein biogenesis, lipid metabolism, and the regulation of transporters. Its dysregulation is associated with neurodegenerative diseases like spinal muscular atrophy and ataxia. Studies using KO/CKO mouse models and other in vivo models have significantly contributed to understanding its role in these disease conditions, providing potential therapeutic targets for related disorders.