Ceramide 1-phosphate binding proteins: emerging regulators of cell physiology and disease.

Ceramide-1-phosphate (C1P), once considered a minor metabolic intermediate, is now recognized as a relevant regulator of cell survival, inflammation, migration, oxidative stress, glucose uptake and adipogenesis. These diverse functions are mediated by direct interactions between C1P and specific protein targets, including enzymes, lipid transfer proteins, and signaling effectors (typically proteins). While C1P was demonstrated to regulate a variety of signaling pathways, including phosphatidylinositol 3-kinase (PI3K)/Akt, mitogen-activated protein kinase kinase (MEK)/extracellularly regulated kinases (ERK) 1-2, or sphingomyelin synthase (SMS)/protein kinase-C-alpha (PKCα), this review namely focuses on the eight major proteins that directly interact with C1P: acidic sphingomyelinase (ASMase), serine palmitoyl transferase (SPT), Ca²⁺-dependent cytosolic phospholipase A 2 -alpha (cPLA 2 α), Gi protein-coupled receptors, C1P transfer protein (CPTP), sphingomyelinase phosphodiesterase like 3b (SMPDL3b), annexin A2-p11 (S100A10), and Kelch-like ECH-associated protein 1 (KEAP1). Understanding C1Pprotein interactions provides a conceptual framework for targeting sphingolipid signaling in inflammation, cancer and metabolic diseases. Here, we summarize current evidence for C1P binding or functional modulation of these proteins, and highlight the implications of these interactions in inflammation, oxidative stress control, and disease pathogenesis.