At its discovery in the 1980s, the proteasome was relegated to the essential but unglamorous role of cellular garbage pail – a last resting place for worn-out, misfolded, or otherwise unwanted proteins. But researchers soon uncovered a host of more specific, and decidedly sexier, roles for the large protein complex. Proteasomal degradation of perfectly good proteins was found to regulate important physiological processes, including cell-cycle progression, inflammatory responses, and antigen presentation.[1] Yet now, as aberrant protein accumulation is being implicated in disease states from Alzheimer disease to multiple myeloma, researchers are considering whether simply taking out the trash is more crucial, and more carefully regulated, than once thought.