Protein misfolding and aggregation is the phenomenon of the generic propensity of
proteins, considered as a dark side of the
protein world, and its exact mechanism is still not deciphered. Understanding the complexity of
protein aggregation is currently the primary apprehension and challenge in biology and medicine due to their association with various debilitating human
proteinopathies and
neurodegenerative diseases. The mechanism of
protein aggregation, associated diseases, and the development of efficient therapeutic strategies against these diseases are very challenging. These diseases are caused by different
proteins, each
protein with different mechanisms and consisting of various microscopic phases or events. These microscopic steps are functioning on different timescales during aggregation. Here, we highlighted the different features and current trends in
protein aggregation. The study thoroughly recapitulates the various factors influencing, possible causes, types of aggregates and aggregation, their different proposed mechanisms, and the methods used to study the aggregation. Additionally, the formation and elimination of misfolded or aggregated
proteins in the cell, the role of the ruggedness of the protein folding landscape in
protein aggregation,
proteinopathies, and the challenges for their prevention are comprehensively elucidated. A holistic understanding of different aspects of aggregation, molecular steps governing the various features of
protein quality control, and crucial queries about the modulation of these processes and their interactions with other systems in cellular
protein quality control can be considered conducive to comprehending the mechanism, designing effective approaches towards prevention of
protein aggregation, rationalizing the etiology and development of novel strategies against
therapy and management of the
proteinopathies.