Circadian rhythm is a physiological mechanism with daily periodicity to adapt to the daily environmental changes. Regulation of circadian rhythm affect behavior (sleep-wake cycle) and other physiological functions. The molecular mechanism of circadian regulation is through the transcription-translation feedback loop. Cryptochrome protein (CRY) and Period protein (PER) play a negative feedback function in the mammalian system. CRY and PER could interact with each other. Thus, they were considered to regulate circadian rhythm as a heterodimer. However, the ratio of CRY and PER proteins are different at different times of the day, suggesting the existence of their independent functions. This talk will focus on introducing the mammalian transcription-translation feedback loop and discuss the independent function of CRY in transcriptional repression based on the research results from in celluo biochemical system in the lab.