TIMELESS (timeless circadian regulator) is a multifunctional protein with critical roles in DNA replication, genome maintenance, and circadian rhythm regulation. Functionally, TIMELESS stabilizes replication forks by forming a complex with TIPIN 1, inhibiting CMG helicase activity while activating DNA polymerases to couple DNA unwinding with synthesis 2. The TIMELESS-TIPIN complex is essential for replisome organization and progression 3, facilitating processive replication through G-quadruplex structures 4. During DNA damage responses, TIMELESS accumulates at double-strand breaks and promotes homologous recombination repair through interaction with PARP1 56, while also participating in the ATR-CHEK1 replication checkpoint 7. Recently, TIMELESS-TIPIN was shown to protect replisomes from transcription-replication conflicts in early S phase 8, and to mediate local replication attenuation at damaged chr12 through prevention of replication initiation in DSB-containing topologically associating domains 9. In circadian regulation, TIMELESS negatively regulates CLOCK-BMAL1-induced transcription and influences period length determination 10. Clinically, elevated TIMELESS expression correlates with poor survival in lung cancer 11, while mutations cause familial advanced sleep phase syndrome 12. The TIMELESS-mediated miR-129-2-3p/ATM/ATR/p53 pathway also contributes to cellular senescence in inflammatory diseases 13.