Nebulette, the cardiac isoform of the giant (>600 kDa) actin-binding protein nebulin (found in skeletal muscle), is localized to, and predicted to extend <150 nm beyond, the Z-disk. Nebulette consists of a short N-terminal domain and 22 nebulin-like repeats that are connected to a C-terminal SH3 domain by a short linker domain (3). Overexpression of the linker or SH3 domains in chicken embryonic cardiomyocytes resulted in a loss of endogenous nebulette and a decrease in filament length (4- 5), suggesting a role for nebulette in both thin filament and Z-disk assembly, function, and stability (3,5- 6). Nebulette interacts with a large number of thin filament-associated and Z-disk–associated proteins (3). The central repeat domains associate with actin, troponin, and tropomyosin; the SH3 domain interacts with actin, α-actinin (7), CapZ, titin, myopalladin, zyxin (8), desmin (9), and filamin C (10).