Entrainment, the synchronization of internal circadian clocks with external light-dark cycles, is crucial for optimal organismal function. In Drosophila melanogaster, the flavoprotein cryptochrome (CRY) plays a central role in light-induced entrainment. CRY initiates the degradation of Timeless (TIM), a key clock protein, for clock resetting. Despite extensive research on CRY's role in TIM degradation, the intricate molecular mechanisms remain unclear. This dissertation focuses on the mechanistic details of Jetlag (JET), an E3 ubiquitin ligase, in mediating TIM degradation by CRY.We established a robust expression system for all components of the CRY:TIM:JET complex. Utilizing Select Western-blot Free Tagged-protein Interaction (SWFTI) assays to map protein-protein interactions, we comprehensively characterized their interactions, paving the way for subsequent purification and structural analysis. Notably, we identified a conserved JET binding site on CRY, similar to that observed in mammalian CRY:JET interactions. Intriguingly, our investigation uncovered a non-canonical role for CRY. SWFTI assays revealed an interaction between CRY and the voltage-gated potassium ion channel β-subunit, Hyperkinetic (HK). Unlike other known CRY interactions in the canonical clock, this novel CRY:HK interaction appears to be independent of light or cofactor binding. This dual functionality of CRY, mediating both circadian light entrainment and potentially influencing neuronal activity through HK, suggests a broader role for CRY in brain function.