Autophagy–lysosomal pathway (ALP)

The **autophagy–lysosomal pathway** is a cellular degradation system wherein cytoplasmic material—including damaged organelles and proteins—is delivered to and broken down by the lysosome[1][3][5]. The most studied form, macroautophagy, involves the formation of a double-membraned autophagosome that engulfs cellular cargo and then fuses with the lysosome for degradation; related processes include microautophagy and chaperone-mediated autophagy, both of which also use lysosomal degradation as a final step[1][5][9]. This pathway regulates cellular homeostasis, provides substrates during nutrient deprivation, and removes toxic aggregates, making it central to cell survival, adaptation, and turnover[5][3]. Dysregulation is connected with a variety of disease states, especially **neurodegeneration**, **cancer**, and **infection**, and therapeutic interest is focused on manipulating either autophagy initiation or lysosomal degradation directly using small molecules and biologics[2][6][4]. However, "autophagy–lysosomal pathway" refers to a network of interconnected processes rather than a single molecular target or receptor, so it is not a canonical therapeutic “target” in the strict pharmacological sense[2][6].

Other names

Autophagy–lysosome pathwayAutophagy-lysosomal systemAutophagy pathwayAutophagic-lysosomal pathway

Inhibition of lysosomal function (e.g., by increasing lysosomal pH or inhibiting hydrolases); Inhibition of autophagy initiation (e.g., ULK1 inhibition); Induction or suppression of autophagosome–lysosome fusion