Abstract: Retinoic acid (RA), the active metabolite of vitamin A (the retinoids), elicits a wide spectrum of biological activities critical to the development and health of most of the organ systems including the nervous systems (Corcoran et al., 2002). The effects of RA are mediated by two very distinct pathways; the first is manifested in the nucleus by binding to a large family of nuclear RA receptors (RARs) to regulate proper expression of RA-targeted genes, and the second occurs in the cytoplasm by binding to a specific cytoplasmic protein named cellular RA binding protein 1 (CRABP1) to modulate specific cytosolic signaling (Nhieu et al., 2022). The RAR-mediated gene-regulatory activity is referred to as “canonical” and is important for many cellular processes such as cell lineage determination, maintenance, differentiation, function, and survival. The CRABP1-mediated activity of RA is referred to as “non-canonical”, characterized by its rapid, transient, and modulatory feature (Nhieu et al., 2022). While this CRABP1-mediated non-canonical activity of RA was established only recently, it has been increasingly supported by accumulated evidence in recent studies of Crabp1 knockout (CKO) mice.