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. This evidence concerns the gene ENO1 and nephrolithiasis.