A key for proper functioning of proteins require, its correct localization and proper folding within the crowded cellular milieu. The correct folding of protein is needed for it perform several critical cellular functions and a misfolded protein is highly inclined to aggregate and cause cellular pathological changes. The cellular machinery which performs the task of ensuring proper protein folding and also removal of misfolded aberrant proteins from the cells is known as cellular protein quality control system. This machinery is made up of different components like ubiquitin proteasome system, autophagy and chaperones. In many of the pathologies associated with protein misfolding, a loss in the functions of the different components of PQC is observed, since the misfolded protein sequester the functional proteins of PQC and cause a defect in their function. Hence it becomes critical to understand the molecular mechanisms which lead to defects in the PQC components. To comprehend this query, here, in this study we have considered four mutant proteins of Huntington (HD74Q), spinocerebellar ataxia (Atx84Q), amyotrophic lateral sclerosis (SOD1G37R) and a putative misfolded model protein of chloramphenicol-acetyltransferase (DELTA9CAT), as these proteins tend to misfold and thus form aggregates in the cell. We have analysed how these misfolded proteins can sequester functional proteins of protein quality control system like Hsp70, p62, CHIP and E6-AP in healthy and also in various types of stress conditions. During this work, various types of molecular biology, cell culture methods, biochemistry and microbiology related techniques and tools were used. Taken together, this study suggest that there exists a robust and intricate protein quality control system as a cellular defense mechanisms against proteotoxic stress and it can be useful in future for the development of molecular therapeutic approaches to counter protein misfolding problems.