Cellular retinoic acid-binding protein (CRABP)

Cellular retinoic acid-binding proteins (CRABPs) are small, highly conserved cytosolic proteins that bind all-trans-retinoic acid (atRA) with high affinity. They serve as essential regulators of vitamin A metabolism and signaling by controlling the intracellular trafficking and bioavailability of atRA. The two primary isoforms, CRABP1 and CRABP2, have distinct but complementary roles: CRABP2 is largely responsible for delivering atRA to nuclear receptors to drive gene expression, while CRABP1 is involved in sequestering atRA and modulating non-canonical signaling pathways like MAPK and CaMKII. In clinical contexts, CRABPs are significant therapeutic targets and biomarkers in various cancers, where their expression levels often correlate with tumor progression and sensitivity to retinoid-based therapies. Furthermore, recent research highlights their potential as targets in neurodegenerative diseases, such as ALS, by modulating protein kinase activity to mitigate excitotoxicity and cell death.

Other names

CRABP-ICRABP-IICRABPICRABPIIRBP5RBP6Cellular retinoic acid-binding protein 1Cellular retinoic acid-binding protein 2

CRABPs act as intracellular chaperones for all-trans-retinoic acid (atRA). CRABP2 facilitates the transport of atRA from the cytosol to the nucleus, where it delivers the ligand to retinoic acid receptors (RARs) to initiate gene transcription. CRABP1 primarily sequesters atRA in the cytoplasm to regulate its bioavailability and catabolism, and it also mediates non-canonical signaling by interacting with and modulating cytosolic kinases such as CaMKII and MAPK.