Stress granules (SGs) and P-bodies (PBs) are paradigm biomolecular condensates, also referred to as membraneless organelles [1]. They consist largely of non-translating mRNA-protein complexes (mRNPs), and their assembly, composition, dynamics, and function has been the focus of considerable research effort and speculation for almost 25 years [2], [3], [4], [5], [6]. In contrast, how SGs and particularly PBs undergo clearance in cells, either via disassembly or degradative means is less well understood, though many pathways and factors have been implicated. SG and PB clearance mechanisms help determine SG and PB abundance, understanding of which may reveal new functional insights, and be pertinent to understanding the dynamics and function of other biomolecular condensates. Additionally, SG clearance defects are linked to the pathogenesis of Amyotrophic Lateral Sclerosis (ALS) and other neurodegenerative diseases [7], [8], [9]. Thus, understanding SG and PB clearance may identify future therapeutic targets.

In this review, I will discuss reported and putative mechanisms of SG and PB clearance, assess the importance and integration of distinct clearance pathways, identify gaps in knowledge, and suggest future experimental priorities. A quantitative summary of reported SG and PB clearance effects is presented in Table S1 for additional reference. Finally, a simple working model of SG clearance will be presented.