Cellular Retinoic Acid Binding Protein 1 (CRABP1) is a mediator of non-canonical activities of retinoic acid (RA). It forms complexes with specific signaling molecules, functioning as RA-regulated signalsomes in a cell-context-dependent manner. CRABP1 is involved in multiple pathways, such as regulating MAPK and CaMKII activities, which are associated with stem cell proliferation, cancers, adipocyte health, neuro-immune regulation, heart and motor neuron diseases [1].

Crabp1 knockout (CKO) mouse models have been instrumental in revealing its functions. CKO mice exhibit an adult-onset ALS-like phenotype with deteriorated neuromuscular junctions, indicating CRABP1's role in maintaining neuromuscular junctions through the CRABP1-CaMKII-Agrn signaling pathway [3]. They also show altered exosome profiles, suggesting a novel function of CRABP1 in modulating exosome secretion [2]. Additionally, CKO mice have reduced anxiety-like behaviors, altered HPA axis feedback inhibition due to changes in FKBP5 expression [4], and develop hypertrophy with elevated CaMKII phosphorylation, making them more susceptible to isoproterenol-induced cardiac injury [6]. Ablation of ARCCRABP1 neurons (neurons expressing CRABP1 in the arcuate nucleus) in mice leads to obesity and a diabetic phenotype, demonstrating their role in energy homeostasis regulation [5].

In conclusion, CRABP1 is crucial for multiple biological processes. Studies using CKO mouse models have revealed its significance in diseases like ALS, heart diseases, and stress-related disorders, as well as in physiological functions such as exosome secretion and energy homeostasis regulation. These findings provide valuable insights into the mechanisms underlying these conditions and potential therapeutic targets.