MicroProteins are small, single-domain proteins that dimerize with larger multi-domain proteins andprevent them from forming functional complexes. To date, 22 microProteins have been identified inplants that regulate their target by sequestering them into non-productive protein complexes. The twoorthologous microProteins, miP1a and miP1b were identified using a computational analysis. MiP1aand miP1b are small B-Box containing proteins that interact with and negatively regulateCONSTANS (CO), a major regulator of flowering in Arabidopsis thaliana. They are known to be thefirst microProteins that regulate their target by forming a higher order protein complex. They forman at least trimeric complex with CO and the transcriptional repressor TOPLESS (TPL). Ectopicexpression of miP1a or miP1b in plants causes a late flowering phenotype, due to the failure in COdependentactivation of FLOWERING LOCUS T (FT) expression. In agreement with the lateflowering of overexpression plants, loss-of-function mutants of both miP1a and miP1b, generatedusing CRISPR/Cas9 genome engineering, showed also a slightly early flowering phenotype. In aforward genetic screen using transgenic plants overexpressing miP1a, we isolated a mutant with asplice site mutation in the JUMONJI 14 (JMJ14) gene that strongly suppressed the ability of miP1ato delay flowering. JMJ14 encodes a histone demethylase known to repress flowering, suggesting itcould be part of the microProtein repressor complex. We showed that JMJ14 is involved in theepigenetic regulation of FT that is initiated by the repressive function of the miP1a/CO/TPL complex.Currently all identified and characterized microProteins regulate transcription factors. Using acomputational approach novel microProtein candidates were identified in several sequenced genomesthat may disturb the complex formation of a wider range of multi-domain proteins. In Arabidopsisthaliana conserved putative microProteins were identified and classified into protein classesdependent on their putative ancestor and protein-protein-interaction (PPI) domain. Using a syntheticmicroProtein approach, we demonstrate that microProteins are able to regulate multi-domain proteinsbelonging to different protein classes. Furthermore, these results revealed that microProteins mayprovide a useful tool for post-translational regulation due to their role in protein regulation.