Substrate-recognition component of the SCF(FBXL21) E3 ubiquitin ligase complex involved in circadian rhythm function. Plays a key role in the maintenance of both the speed and the robustness of the circadian clock oscillation. The SCF(FBXL21) complex mainly acts in the cytosol and mediates ubiquitination of CRY proteins (CRY1 and CRY2), leading to CRY proteins stabilization. The SCF(FBXL21) complex counteracts the activity of the SCF(FBXL3) complex and protects CRY proteins from degradation. Involved in the hypothalamic suprachiasmatic nucleus (SCN) clock regulating temporal organization of the daily activities. Protein modification; protein ubiquitination. Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL21) composed of CUL1, SKP1, RBX1 and FBXL21. Interacts with CRY1 and CRY2. Mainly localizes in the cytosol. Present at low level in the nucleus. Expressed in the hypothalamus, especially in the suprachiasmatic nucleus (SCN). Expression is driven by the core-clock. There is a pronounced diurnal and circadian expression rhythms rising rapidly at the start of the day and declining at the onset of the night. Mice show normal periodicity of wheel-running rhythms with compromised organization of daily activities: mice do not display significant difference from their wild-type littermates in both the free-running period in constant darkness (DD) and activity onset in 12 hours of light/12 hours of darkness (LD). However, an alteration in the daily activities is observed: while wild-type mice show 2 peaks of activity during the active period, the late night activity is eliminated in Fbxl21-deficient mice. Mice lacking both Fbxl3 and Fbxl21 show an attenuated phenotype in behavioral rhythm compared to Fbxl3-deficient mice; however, they exhibit unstable behavioral rhythms, sometimes eliciting arrhythmicity. The mechanism by which the SCF(FBXL21) complex stabilizes CRY proteins (CRY1 and CRY2) is still unclear: according to a report, the SCF(FBXL21) complex does not catalyze 'Lys-48'-linked polyubiquitin chains, but catalyzes a different type of ubiquitin chains that do not lead to degradation (PubMed:23452856). According to a second report, FBXL21 has a higher affinity for CRY proteins compared to FBXL3, while the SCF(FBXL21) complex has weaker ubiquitin-ligase activity compared to the SCF(FBXL3) complex: as a consequence, the SCF(FBXL21) complex protects CRY proteins from SCF(FBXL3) activity and degradation in the nucleus, while it promotes slow degradation of CRY proteins in the cytosol (PubMed:23452855). Truncated N-terminus.