The ubiquitin-proteasome system (UPS) and autophagy are two major degradative pathways in eukaryotic cells. Their precise functioning and tight regulation are indispensable. Dysregulation of these pathways is associated with various diseases such as neurodegenerative disorders and cancer. However, the mechanisms underlying their complementary reciprocal relationship remain unclear. Dictyostelium discoideum, a well-established model organism for autophagy research that also possesses a well-characterised proteasome system, has been used in our studies. We observed a marked increase in proteasomal activity upon inhibition of autophagy, and conversely, enhanced autophagic activity when the proteasome was inhibited. This suggests the existence of a compensatory reciprocal mechanism, wherein one degradation pathway compensates for the loss of the other. Additionally, treatment with MG132 (a proteasomal inhibitor) resulted in the formation of abnormal fused structures resembling those seen in autophagy mutants during Dictyostelium development, indicating an interplay between the UPS and autophagy in cellular development. Furthermore, p62 (SQSTM1), an autophagy receptor also known to transport ubiquitinated proteins for proteasomal degradation, has been shown in other model organisms to play a regulatory role in maintaining the balance between these two pathways. Our studies on p62 knockout strain in Dictyostelium showed reduced autophagic and proteasomal activities with an imbalance in reciprocal complementarity between the two degradative pathways, indicating p62 as a major regulatory link between both degradation systems. Further studies, including the investigation of genes associated with both pathways will help understand their co-regulation, which may lead to the identification of novel therapeutic targets playing a key role in co-regulation.