Sigma RECEPTORS, UNIQUE RECEPTORS GENERALLY IDENTIFIED AND CLASSIFIED AS OPIOID AND PHENCYCLIDINE (PCP) RECEPTORS, ARE SMALL MEMBRANE PROTEINS CONCERNED IN SEVERAL PATH PHYSIOLOGICAL CONDITIONS, INCLUDING CANCER, DRUG ADDICTION, AND PSYCHOSIS; THUS, SMALL MOLECULE INHIBITORS OF Sigma RECEPTORS HAVE BEEN SUGGESTED AS POTENTIAL PHARMA COTHERAPEUTICS FOR THESE DISEASES. TWO SUBTYPES OF THE Sigma RECEPTOR HAVE BEEN DEFINED, TERMED Sigma-1 AND Sigma-2, WHICH CAN BE DISTINGUISHED BY THEIR PHARMACOLOGICAL PROFILES, FUNCTIONS, MOLECULAR WEIGHT, LOCATIONS SELECTIVITY, AND SUBCELLULAR. Sigma-1 RECEPTOR BASICALLY SHOW MODULATORY PROPERTIES, FOR EXAMPLE, MODULATION OF CHLORIDE (CL-), CALCIUM (CA2+), SODIUM (NA+), POTASSIUM (K+), COMPARTMENTALIZATION OF LIPID ON THE ENDOPLASMIC RETICULUM, "LIGAND-OPERATED" CHAPERONING ACTIVITY AT MAM, AND Sigma-1 RECEPTOR BINDING OF CHOLESTEROL IN LIPID RAFTS REGARDING THE PROLIFERATION OF CANCER CELLS. IN THIS ARTICLE WE PROVIDE AN OVERVIEW OF THE PRESENT UNDERSTANDING OF Sigma RECEPTOR, FOCUSING ON BINDING AND SYNTHESIS OF Sigma LIGANDS, CHARACTERIZATION BINDING SITE ON THE Sigma-1 RECEPTOR, PROBING THE STEROID BINDING DOMAIN-LIKE I AND II, AND EVIDENCE OF RECEPTOR DIMMERS.