I already know one method of doing so, but it's inelegant:

use constant ENABLE_DEBUG => 0;
sub debug { print $_[0]; }
debug 'test' if ENABLE_DEBUG;
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You can see the call gets optimized away in the Deparse output:

use constant ('ENABLE_DEBUG', 0);
sub debug {
    print $_[0];
}
'???';
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However, the more elegant equivalent...

use constant ENABLE_DEBUG => 0;
sub debug { print $_[0] if ENABLE_DEBUG(); }
debug 'test';
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...does not get optimized away:

use constant ('ENABLE_DEBUG', 0);
sub debug {
    0;
}
debug 'test';
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Update 1: diotalevi convinced me to use constant. Update 2: I stumbled on Smart::Comments, which is very interesting, but I don't know if it could be made to work with Log::Log4perl. Plus, it's a source filter (take that as you will).