You didn’t say what you wanted to replace it with. But it’s pretty easy to do with regular expressions.

Your FindWhat should be ,(.*)$: this says find a comma, then store the rest of the line in group $1 (aka \1). Your replacement would then be ::$1 if you wanted to replace that first comma with ::; the literal characters are replaced as-is, and the $1 brings back the group1, which was the rest of the line from the original match.

With your example data

test1,test2,test3
test4,test5,test6

that results in

test1::test2,test3
test4::test5,test6

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Some boilerplate that I usually add the first time I respond to a new user’s search/replace question:

This forum is formatted using Markdown, with a help link buried on the little grey ? in the COMPOSE window/pane when writing your post. For more about how to use Markdown in this forum, please see @Scott-Sumner’s post in the “how to markdown code on this forum” topic, and my updates near the end. It is very important that you use these formatting tips – using single backtick marks around small snippets, and using code-quoting for pasting multiple lines from your example data files – because otherwise, the forum will change normal quotes ("") to curly “smart” quotes (“”), will change hyphens to dashes, will sometimes hide asterisks (or if your text is c:\folder\*.txt, it will show up as c:\folder*.txt, missing the backslash). If you want to clearly communicate your text data to us, you need to properly format it.

If you have further search-and-replace (“matching”, “marking”, “bookmarking”, regular expression, “regex”) needs, study this FAQ and the documentation it points to. Before asking a new regex question, understand that for future requests, many of us will expect you to show what data you have (exactly), what data you want (exactly), what regex you already tried (to show that you’re showing effort), why you thought that regex would work (to prove it wasn’t just something randomly typed), and what data you’re getting with an explanation of why that result is wrong. When you show that effort, you’ll see us bend over backward to get things working for you. If you need help formatting, see the paragraph above.

Please note that for all regex and related queries, it is best if you are explicit about what needs to match, and what shouldn’t match, and have multiple examples of both in your example dataset. Often, what shouldn’t match helps define the regular expression as much or more than what should match.