Abstract
In most organisms, cell‐autonomous circadian clocks are driven by a transcription–translation negative feedback loop (TTFL). Per was the first identified clock gene in the fruit fly and is a core component of the circadian TTFL. Surprisingly, in their recent study, Rey et al (2018) demonstrate the presence of apparent circadian rhythmicity in a fly cell line that does not express several core clock genes including per (Rey et al, 2018). Quantitative multi‐omics measurements allowed the identification of unknown oscillating components and revealed hundreds of transcripts, proteins, and metabolites showing 24‐h rhythmicity, suggesting that at least in the fly, the circadian clock may be driven by non‐canonical (i.e., independent of per‐driven TTFL) molecular mechanisms.