With significant advancements in the study of DNA Damage Response (DDR) and Fanconi Anemia (FA) signaling, we previously introduced the term “FA signaling” to encompass “all signaling transductions involving one or more FA proteins.” This network has now evolved into the largest cellular defense network, integrating over 30 key players, including ATM, ATR, BLM, HRR6, RAD18, FANCA, FANCB, FANCC, BRCA2, FANCD2, FANCE, FANCF, FANCG, FANCI, BRIP1, FANCL, FANCM, PALB2, RAD51C, SLX4, ERCC4, RAD51, BRCA1, UBE2T, XRCC2, MAD2L2, RFWD3, FAAP20, FAAP24, FAAP100, and CENPX. The gene discussed is MAD2L2; the disease is Fanconi anemia.