Our major discoveries include: (1) discovered previously unappreciated lysosome localization of ABHD5, shedding light on a novel role of ABHD5 in lysosome function; (2) ABHD5 competes with RNASET2 to directly interact with PDIA5; (3) ABHD5 deficiency releases PDIA5 to directly interact with RNASET2 and leave RNASET2 in an inactivate state, which impairs RNASET2-induced autophagic uracil yield; (4) ABHD5 deficiency promotes CRC cells to uptake FU as an exogenous uracil, thus increasing their sensitivity to FU. The gene discussed is RNASET2; the disease is colorectal carcinoma.