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Cryptochromes, evolutionally conserved and retained in mammals as transcriptional regulators having a repressive role in the transcription-translation feedback loop, the molecular mechanism behind the control of the endogenous mammalian circadian clock. This clock mechanism regulates the oscillation of a huge number of clock-controlled output genes. This in turn is responsible for modification of the physiological response of most organs and tissues, to coordinate with diurnal and seasonal changes in light and nutrient availability. Cryptochromes have also been found to participate in additional signalling cascades, outside of the circadian system, forming supplementary feedback loops that initiate cross-talk between systems influencing metabolism, inflammation and DNA damage response to maintain cellular homeostasis. This physiological organisation system has developed from Palaeolithic man but is still relevant in our modern world.