Because crystal invasion is a crucial step of kidney stone formation and enolase-1 can bind to both COM crystal9 and plasminogen10 and then activate plasmin activity to degrade ECM, we have thus hypothesized that enolase-1 is one of the important secreted proteins that triggers crystal invasion through the renal interstitium using its capability to bind to both COM crystal and plasminogen. The gene discussed is PLG; the disease is nephrolithiasis.