Over the past several years, many groups worldwide have confirmed the presence of probable disease-causing mutations in the coding region of the (TIGR/MYOC) gene associated with glaucoma. Disease-associated point mutations are often found in the third exon of TIGR/MYOC and are predicted to exert a substantial influence on protein structure. Although there has been speculation as to the mechanisms involved in the pathogenic effects for a number of the mutations, the processes leading to the development of glaucoma involving TIGR/MYOC remain to be elucidated. In addition to ongoing mutation studies, efforts are underway to follow up on TIGR/MYOC gene regulation studies in human trabecular meshwork cells and other possibly relevant cell types. Potentially by altering gene regulation, a major variant (-1000 G/C), present in 15-20% of individuals, appears to be associated with a more rapid progression of glaucomatous disease. This article addresses several of these areas of research on the TIGR/MYOC gene and glaucoma, briefly presenting currently available evidence and considering or updating information presented previously.