This thesis investigates the role of Transglutaminase-2 (TG2) in acute promyelocytic leukemia (APL), particularly how it interacts with the PML-RARα fusion protein and affects retinoic acid (RA) signaling pathways. By treating NB4 cells with all-trans retinoic acid (ATRA), we were able to trigger the movement of TG2 into the nucleus, which allowed us to detect, isolate, and study it. We used various biochemical methods like cell fractionation, co-immunoprecipitation, and isoelectric focusing to explore TG2’s interactions with other nuclear proteins. Our findings show that TG2 plays a significant role in the differentiation and apoptosis of APL cells, rendering it a therapeutic target. This research adds to our understanding of TG2’s importance in both APL and broader cellular functions.